Substituted dioxolanes and process for their production



United States Patent ()1 3,294,818 SUBSTITUTED DIOXOLANES AND PROCESSFOR THEIR PRODUCTION George Bobowski, East Grange, John Shavel, In,Mendham, and Maximilian von Strandtmann, Rockaway Township, N.J.,assignors to Warner-Lambert Pharmaceutical Company, Morris Plains, Ni, acorporation of Delaware No Drawing. Filed Apr. 6, 1964, Ser. No. 357,798

2 Claims. (Cl. 260-3409) This invention relates to a new and novelsubstituted 1,3-propanediol of the formula:

with ethylene glycol in the presence of p-toluenesulfonic acid in aninert anhydrous solvent such as anhydrous benzene or xylene.

The starting material used in the above reaction is described andclaimed in copending application Serial No. 231,027, now Patent No.3,183,265.

The reaction is completed over a period of about 12 hours during whichthe -(ILJ-OHOI2 attached to the amino group is split 011 and results inthe formation of D-threo-1-[p-2(cyclohexyl-1,3-dioxolan-2-yl)phenyl]-2-amino-l,3-propanediol. The latter is generally notisolated but is treated directly with an excess of methyldichloroacetateto yield the desired D- threo-1-[p-2(cyclohexyl 1,3 dioxolan 2yl)phenyl]- 2-(2,2-dichloroacetamido) 1,3 propanediol of this invention,the structural formula of which appears above. The

Patented Dec. 27, 1966 ICC reaction product may be recovered from thereaction medium by evaporating the solvent in vacuo.

For therapeutic use the compound of this invention may be combined inthe standard pharmaceutical eX cipients to give dosage forms such astablets, suspensions, and the like.

The following example is included in order further to illustrate theinvention.

A solution of 0.75 g. ofD-threo-l-(p-cyclohexylcarbonyl)-2-(2,2-dichloroacetamido)1,3-propanediol, 4.0 ml. of ethylene glycol and 0.1 g. ofp-toluenesulfonic acid in ml. of anhydrous benzene is refluxed for 12hours resulting in the separation of 0.25 ml. of water. After coolingthe reaction mixture to 0 C. it is treated With ammonia and the twophases are separated. The organic layer is dried over sodium sulfate,and the solvent is removed in vacuo. The residual gum is refluxed with3.0 ml. of methyldichloroacetate in 50 ml. absolute ethanol for 4 hours.The solvent and excess reagent are removed in vacuo to give 0.75 g. ofD-threo-l-[p- 2-(cyclohexyl-1,3-dioxolan-2-yl)phenyl] 2(2,2-dichloroacetamido)-l,3-propanediol as a light-brown semisolid. Tworecrystallizations from ether gives analytically pure, white crystals,M.P. 1l2l13.5 C.;

A523? mu (6) 118 (11,400); 11%;? 808 (m), 1025 (m), 1058 (s), 1107 (m),1530 (s), 1688 (vs), 3320 (s) cmr with? 1050 (s), 1527 (m), 1704 (vs),2850 (m), 2420 (m) cmr Analysis for C H NCl O Calc.: C, 55.56; H, 6.29;Cl, 16.40. Found: C, 55.59; H, 6.52; Cl, 16.32, 16.54.

It is understood that the foregoing detailed description is given merelyby Way of illustration and that many variations may be made thereinWithout departing from the spirit of our invention.

Having described our invention, what we desire to secure by LettersPatent is:

1. D-threo-l-[p-2=(cyclohexyl 1,3 dioxolan 2-yl) phenyl] -2-2,2-dichloroacetamido) 1,3 -propanediol.

2. D-threo-1-[p-2-(cyclohexyl 1,3 dioxolan 2 yl)phenyl]-2-arnino-l,3-propanediol.

OTHER REFERENCES Migrdichian, Organic Synthesis, vol. 1 (1957), pp. 376

and 377, Reinhold Publ. Corp., New York, NY.

ALEX MAZEL, Primary Examiner.

I. H. TURNIPSEED, Assistant Examiner.

1. D-THREO-1- P-2-(CYCLOHEXYL - 1,3 - DIOXOLAN - 2-YL)PHENYL!-2-(2,2-DICHLOROACETAMIDO)1,3-PROPANEDIOL.